Distinct roles of Chk and Csk in regulation of Src family kinases in hematopoietic cells

Chk 和 Csk 在造血细胞 Src 家族激酶调节中的不同作用

基本信息

  • 批准号:
    09671124
  • 负责人:
  • 金额:
    $ 1.98万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    1997
  • 资助国家:
    日本
  • 起止时间:
    1997 至 1998
  • 项目状态:
    已结题

项目摘要

Src family protein-tyrosine kinases play crucial roles in regulating proliferation and differentiation of multiple cell types including hematopoietic cells. The activity of Src family kinases is tightly regulated by tyrosine phosphorylation and dephosphorylation events. The C-terminal Src kinase (Csk), which is expressed ubiquitously, has been shown to phosphorylate the C-terminal negative regulatory tyrosine residue of Src family kinases and suppress their kinase activity. A second member of the Csk family expressed in hematopoietic cells was recently identified as the Csk homologous kinase (Chk).To understand the significance of co-expression of Chk and Csk in hematopoietic cells, we examined the subcellular localization of each protein. Chk but not Csk was localized close to CD36 (membrane glycoprotein IV)-anchored Lyn, and the kinase activity of Lyn was selectively suppressed. Upon stimulation with thrombin, the rapid and complete translocation of Chk away from CD36-anchored Lyn ca … More used concomitant activation of Lyn. The activation was accompanied by dephosphorylation of Lyn at its C-terminal negative regulatory tyrosine in cooperation with a protein tyrosine phosphatase. We propose that Chk but not Csk functions as a translocation-controlled negative regulator of CD36-anchored Lyn in thrombin-induced platelet activation.To further examine die role of Chk in hematopoietic cells, we overexpressed Chk in the megakaryocytic cell line Dami. Overexpression of Chk suppressed VLA5 integrin-mediated cell spreading, but not cell attachment, throughout fibronectin stimulation. This suppression was dependent upon both the SH3 domain, which is responsible for membrane anchoring, and kinase activity. Sustained activation of Lyn, which is regulated by membrane-anchored Chk, was required for VLA5-mediated cell spreading on a fibronectin substrate.Thus, these results suggest that Chk, unlike Csk, negatively regulates Src family kinases in vivo with selectivity toward Lyn and acts as a fine regulator in hematopoietic cells. Less
Src家族蛋白酪氨酸激酶在调节包括造血细胞在内的多种细胞类型的增殖和分化中起着至关重要的作用。Src家族激酶的活性受到酪氨酸磷酸化和去磷酸化事件的严格调节。广泛表达的C-末端Src激酶(Csk)已显示磷酸化Src家族激酶的C-末端负调节酪氨酸残基并抑制其激酶活性。Csk家族的第二个成员在造血细胞中表达,最近被确定为Csk同源激酶(Chk)。为了了解Chk和Csk在造血细胞中共表达的意义,我们检查了每个蛋白的亚细胞定位。Chk而不是Csk被定位在接近于CD 36(膜糖蛋白IV)锚定的林恩,并且林恩的激酶活性被选择性抑制。在凝血酶刺激下,Chk从CD 36锚定的林恩细胞上快速而完全的移位, ...更多信息 同时激活了林恩。该活化伴随着林恩在其C-末端负调节酪氨酸与蛋白酪氨酸磷酸酶合作的去磷酸化。我们认为Chk而不是Csk在凝血酶诱导的血小板活化中作为CD 36锚定的林恩的易位控制负调节剂发挥作用。在整个纤连蛋白刺激过程中,Chk的过表达抑制VLA 5整合素介导的细胞扩散,但不抑制细胞附着。这种抑制依赖于负责膜锚定的SH 3结构域和激酶活性。持续激活的林恩,这是由膜锚定的Chk调节,需要VLA 5介导的细胞在纤连蛋白substrate. Therefore,这些结果表明,Chk,不像Csk,负调控Src家族激酶在体内选择性朝向林恩,并作为一个精细的调节造血细胞。少

项目成果

期刊论文数量(18)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Mera A et al.: "Induction of cell shape changes through activation of the interleukin-3 common beta-chain receptor by the RON receptor-type tyrpsine kinase." J.Biol.Chem.(in press). (1999)
Mera A 等人:“通过 RON 受体型酪氨酸激酶激活白细胞介素 3 常见 β 链受体来诱导细胞形状变化。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Sakamotro O: "Role of macrophase-stimulating protein and its receptor, RON tyrosine kinase, in ciliary motility." J. Clin. Invest.99. 701-709 (1997)
Sakamotro O:“巨相刺激蛋白及其受体 RON 酪氨酸激酶在纤毛运动中的作用。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Hirao A et al.: "Overexpression of C-terminal Src kinase homologous kinase suppresses activation of Lyn tyrosine kinase required for VLA5-mediated Dami cell spreading." J.Biol.Chem.273. 10004-10010 (1998)
Hirao A 等人:“C 端 Src 激酶同源激酶的过度表达会抑制 VLA5 介导的 Dami 细胞扩散所需的 Lyn 酪氨酸激酶的激活。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Tada J: "A common signaling pathway via Syk and Lyn tyrosine kinases generated from capping of the sialomucins CD34 and CD43 in immature hematopojetic cells." Blood. (in press). (1999)
Tada J:“通过未成熟造血细胞中唾液粘蛋白​​ CD34 和 CD43 加帽产生的 Syk 和 Lyn 酪氨酸激酶的常见信号传导途径。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Hirao A: "Translocation of the Csk homologous kinase(chk/Hyl)controls activity of CD36-anchored Lyn tyrosine kinase in thrombin-stimulated platelets." EMBO J.16. 2342-2351 (1997)
Hirao A:“Csk 同源激酶 (chk/Hyl) 的易位控制了凝血酶刺激的血小板中 CD36 锚定的 Lyn 酪氨酸激酶的活性。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
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YAMAGUCHI Naoto其他文献

<b>The Role of Master Carpenters in Improving Informal Settlements</b>
<b>木匠大师在改善非正式住区中的作用</b>
  • DOI:
    10.14398/urpr.9.25
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    0
  • 作者:
    YAMAGUCHI Naoto;Antriyandarti Ernoiz;Irriani Siti Nursanti;SHIMA Norihisa
  • 通讯作者:
    SHIMA Norihisa

YAMAGUCHI Naoto的其他文献

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{{ truncateString('YAMAGUCHI Naoto', 18)}}的其他基金

The prevalenc and associated risk factors for chronic kidney fosease or reduced kidney function in Bangladesh rural.
孟加拉国农村地区慢性肾病或肾功能下降的患病率和相关危险因素。
  • 批准号:
    23406029
  • 财政年份:
    2011
  • 资助金额:
    $ 1.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Is the Lyn-ACSL3 system involved in induction of cell polarization ?
Lyn-ACSL3 系统是否参与细胞极化的诱导?
  • 批准号:
    23659030
  • 财政年份:
    2011
  • 资助金额:
    $ 1.98万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Sorting of tyrosine kinases to organelles and signal transduction
酪氨酸激酶对细胞器的分类和信号转导
  • 批准号:
    21390017
  • 财政年份:
    2009
  • 资助金额:
    $ 1.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Sorting mechanism of subcellular localization of tyrosine kinases and signal transduction
酪氨酸激酶亚细胞定位及信号转导的分选机制
  • 批准号:
    19590057
  • 财政年份:
    2007
  • 资助金额:
    $ 1.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Intracellular trafficking of tyrosine kinases and their differential functions
酪氨酸激酶的细胞内运输及其差异功能
  • 批准号:
    17590053
  • 财政年份:
    2005
  • 资助金额:
    $ 1.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Multinucleation induced by Chk overexpression in hematopoietic cells
造血细胞中 Chk 过表达诱导的多核
  • 批准号:
    11470212
  • 财政年份:
    1999
  • 资助金额:
    $ 1.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B).

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钙粘蛋白 Desmoglein-2 控制细胞扩散和细胞外基质基因表达。
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Beta-1 整合素对生长因子模拟细胞扩散和收缩的形态功能的调节。
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Beta-1 整合素对生长因子模拟细胞扩散和收缩的形态功能的调节。
  • 批准号:
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STOCHASTIC BIOCHEMICAL SIMULATION OF ACTIN-BASED FIBROBLAST CELL SPREADING
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Beta-1 整合素对生长因子模拟细胞扩散和收缩的形态功能的调节。
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